Topology creation for an acylated amino acid in Charmm force field

User discussions
1

GROMACS version: 2023.3
GROMACS modification: No
What is the right way to create a topology for the protein with an acylated amino acid (serine acylated with palmitic acid)?
It seems to be complicated for me, as in the original pdb file serine and PAM are defined separately and the only data that gives ideas about acylation is the link line:
LINK OG SER B 212 C1 PAM B 405 1555 1555 1.45

3

I combined atoms form serine and PAM into one acid in the mol2 file. Then I tried to create the topology for the acylated serine using CGenFF server (as well as for a 3-acid peptide with central serine to get parameters of peptide bonds) and than added parameters to the aminoacids.rtp and to aminoacids.hdb.

IMG_7950
IMG_7951

Now it is possible to run command pdb2gmx, place my protein to the box and solvate it. But when I use grompp command I still get errors: No default Bonds / Dihedral types.
Is it possible to fix it?

4

I have also tried to create topology for PAM separately from serine amino acid (as PAM is ligand) beacause CGenFF server gives 0.0 penalty in such case (compared to ≈18 in the case when modified SER-PAM residue is submitted). But then there is a problem how to create a covalent bond between protein and PAM. Using -merge function and modifying the specbond.dat file didn’t helped me in such case due to differences in H-atoms number before and after bond creation.
Maybe there some other ways to create non-standard residue with right topology?

5

CGenFF will give you the residue parametrized from scratch with CGenFF atom types, while the rest of the protein will have Charmm36/m/ types. In the standard parameter set, there are no parameters for cross-compatibility between these two.

One option is to go to CHARMM-GUI, use PDB Reader, and “Add lipid tail” in step 2. From the dropdown menus, you can choose your preferred modification and the residue to be modified.

A more general solution, e.g. if the desired combination doesn’t show up in CHARMM-GUI, would be to assign the missing bond/angle parameters with Gromologist by analogy, treating CGenFF types as if they were Charmm36 types: